In 2364, the USS Enterprise-D was ordered to investigate the Neutral Zone to solve a mystery concerning the disappearance of a string of Federation outposts. It was later established that the outposts were decimated by the Borg due to a signature obliterative technique unique to their technology. A crew member aboard the ship, Worf, describes it: "The outpost was just not destroyed, it's as though some great force just scooped it off the face of the planet." Later that year, the Enterprise-D encountered a Borg cube that had obliterated several other populations in uncharted space in the same fashion. (TNG: "The Neutral Zone", "Q Who")

In 2366, after receiving intel from a Romulan defector about a possible Romulan base at Nelvana III, outposts along the zone received warnings from Starfleet Command. Several independent vessels in nearby sectors received the same warning. (TNG: "The Defector")